The topological properties of enveloped viruses and cell membranes will be utilized to study membrane fusion of the virus envelope with cell membranes and to study the interactions involved in the process of virus budding from cell membranes. The kinetics of fusion of influenza and parainfluenza virus envelopes with erythrocyte membranes can be studied using virus containing labeled phospholipids on the interior surface of the envelope lipid bilayer. When the asymmetrically labeled virus fuses with membranes that are freely permeable, such as erythrocyte ghosts, the radiolabeled lipids become accessible to reaction with reagents to which the virus envelope is impermeable. The structure of viral envelope components incorporated into erythrocyte membranes by envelope fusion will be studied as a model for membrane interactions involved in the process of virus budding. The questions to be addressed include (1) whether the viral spike glycoproteins penetrate through the lipid bilayer to the cytoplasmic surface, (2) the nature of the interaction of the viral interior membrane nonglycosylated (M) protein with cell membranes, and (3) whether viral nucleocapsids will bind to membranes containing viral envelope components. The advantage to using the erythrocyte membrane, as in the above study of envelope fusion, is that the interior surface of the membrane is accessible to experimental manipulation. In order to extend these structural studies to mature viral envelopes, procedures will be developed for making the envelope permeable and then releasing it, analogous to the ability to reseal erythrocyte ghosts, thus allowing selective access to the interior surface.